Ischemic stroke with cancer: Hematologic and embolic biomarkers and clinical outcomes

• Published in: Journal of thrombosis and haemostasis 2022-09, Vol.20 (9), p.2046-2057
• Main Authors: Navi, Babak B., Zhang, Cenai, Sherman, Carla P., Genova, Richard, LeMoss, Natalie M., Kamel, Hooman, Tagawa, Scott T., Saxena, Ashish, Ocean, Allyson J., Kasner, Scott E., Cushman, Mary, Elkind, Mitchell S. V., Peerschke, Ellinor, DeAngelis, Lisa M.
• Format: Article
• Language: English
• Subjects: Adult; Antithrombin; Antithrombins; Biomarkers; Cancer; Cell adhesion molecules; Clinical outcomes; Death; Humans; Ischemia; Ischemic Stroke - diagnosis; neoplasms; Neoplasms - complications; P-Selectin; Solid tumors; Stroke; Thrombin; Thromboembolism; Thrombomodulin; thrombophilia; thrombosis; Ultrasound
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.15779

Background Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death. Objectives To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes. Methods We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72–120 h after stroke onset. A 30‐min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D‐dimer, thrombin‐antithrombin), platelet (P‐selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule‐1 [sICAM‐1], soluble vascular cell adhesion molecule‐1 [sVCAM‐1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes. Results During an estimated median follow‐up time of 48 days (IQR, 18–312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D‐dimer (HR 1.6; 95% CI 1.2–2.0), P‐selectin (HR 1.9; 95% CI 1.4–2.7), sICAM‐1 (HR 2.2; 95% CI 1.6–3.1), sVCAM‐1 (HR 1.6; 95% CI 1.2–2.1), and microemboli (HR 2.2; 95% CI 1.1–4.5) were associated with the primary outcome, whereas thrombin‐antithrombin and thrombomodulin were not. D‐dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0–1.5). Results were generally consistent in analyses adjusted for important prognostic variables. Conclusions Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer‐related stroke.